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BACKGROUND Cav1.3 voltage-gated L-type calcium channels (LTCCs) are part of postsynaptic neuronal signaling networks. They play a key role in brain function, including fear memory and emotional and drug-taking behaviors. A whole-exome sequencing study identified a de novo mutation, p.A749G, in Cav1.3 α1-subunits (CACNA1D), the second main LTCC in the brain,(More)
Blockade of the N-methyl-D-aspartate receptor by uncompetitive antagonists has implications for symptomatic and neuroprotective therapy of various neuropsychiatric diseases. Since the three-dimensional (3D) structure of this ion channel is unknown, the structural requirements for uncompetitive inhibition were investigated by application of a three-step(More)
The prediction of blood-brain barrier permeation is vitally important for the optimization of drugs targeting the central nervous system as well as for avoiding side effects of peripheral drugs. Following a previously proposed model on blood-brain barrier penetration, we calculated the cross-sectional area perpendicular to the amphiphilic axis. We obtained(More)
Alkaloids isolated from Sarcococca saligna significantly inhibit acetyl- and butyrylcholinesterase enzyme, suggesting discovery of inhibitors for nervous-system disorders. Studying interactions with the active site of the AChE enzyme from Torpedo californica, we have identified hydrophobic interactions inside the aromatic gorge area as the major stabilizing(More)
Daunomycin is one of the most important agents used in anticancer chemotherapy. It interacts with DNA through intercalation of its planar chromophore between successive base pairs. The effect of intercalation on structure, dynamics and energetics is the topic of a wealth of scientific studies. In the present study, we report a computational examination of(More)
Streptococcus (S.) pneumoniae is a major cause of secondary bacterial pneumonia during influenza epidemics. Neuraminidase (NA) is a virulence factor of both pneumococci and influenza viruses. Bacterial neuraminidases (NAs) are structurally related to viral NA and susceptible to oseltamivir, an inhibitor designed to target viral NA. This prompted us to(More)
The structure of human Janus kinase 2 (JAK2) comprising the two C-terminal domains (JH1 and JH2) was predicted by application of homology modelling techniques. JH1 and JH2 represent the tyrosine kinase and tyrosine kinase-like domains, respectively, and are crucial for function and regulation of the protein. A comparison between the structures of the two(More)
The imminent threat of influenza pandemics and repeatedly reported emergence of new drug-resistant influenza virus strains demonstrate the urgent need for developing innovative and effective antiviral agents for prevention and treatment. At present, influenza neuraminidase (NA), a key enzyme in viral replication, spread, and pathogenesis, is considered to(More)
At present, neuraminidase (NA) inhibitors are the mainstay of pharmacological strategies to fight against global pandemic influenza. In the search for new antiviral drug leads from nature, the seed extract of Alpinia katsumadai has been phytochemically investigated. Among the six isolated constituents, four diarylheptanoids showed in vitro NA inhibitory(More)